Abstract

Bisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.8±6.8 to 69.1±10.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.6±8.4 to 47.1±7.5 ng/ml, P<0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.039±0.002 to 0.043±0.001 ng/10(6) cells, P<0.01), but decreased with polynephron dialyzers (from 0.045±0.001 to 0.036±0.001 ng/10(6) cells, P<0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro, polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.

Study design. (A and B) In this crossover study, prevalent patients on hemodialysis were evaluated and sampled at baseline and next switched to a different dialysis membrane for 3 months. At that point, samples were taken and the membrane switched to the baseline one. (C) At 6 months, new sampling took place.

Correlation between serum BPA levels and inflammatory markers. Mean values for each group and time point are shown. BPA and inflammatory markers (A) CRP and (B) IL-6 were assessed in the same samples. Dashed lines represent timelines for the two independent groups. The first data point (B) along the dashed line represents baseline values, the second (3) the 3-month time point, and the third (6) the 6-month time point. Arrows represent the sequence of dialyzers. The dialyzer is color-coded. This was a crossover study of prevalent patients on hemodialysis and each independent study group was dialyzed at baseline with a different dialyzer. Thus, one group changed from polysulfone at baseline to polynephron and back to polysulfone, and the other group changed from polynephron at baseline to polysulfone and back to polynephron.